Previous reports have suggested that localized alterations in brain metabolism occur after administration of ethanol as well as other drugs. General and localized changes in metabolic activity within the brains of rats exposed to various drugs capable of producing physical dependence were studied using the 2-deoxyglucose technique. Specifically, we have studied the chronic administration and subsequent withdrawal as well as the acute effects of ethanol, phenobarbital, diazepam and various peptides on brain glucose metabolism. Similarities and differences were noted in the autoradiographs from rats undergoing withdrawal from ethanol, phenobarbital and diazepam. Among the similarities were the appearance of columns in the frontal sensorimotor cortex and ovoid areas in the cerebellar vermis. The administration of 5 mg/kg of diazepam to an ethanol withdrawing rat resulted in supression of behavioral withdrawal signs and a loss of columnar and ovoid areas in resulting 2-DG autoradiographs. A general decrease in glucose metabolism was noted in Sprague- Dawley rats given ethanol acutely with an increase in metabolism seen in only the superior olive and dentate region of the hippocampus at a blood ethanol concentration of 14 mM. Differences in glucose metabolism were noted in rats that were bred to prefer or not prefer ethanol. Further experiments and analysis is needed to illustrate a genetic basis for these differences. Experiments are progressing to investigate the effect of various peptides especially peptide T and related peptides on brain metabolism, using peptide sequences common to the AIDS virus envelope proteins and VIP.